Among patients with renal insufficiency secondary to autosomal dominant polycystic kidney disease (ADPKD), the onset of refractory urinary infection, hypertension, pain, or hematuria often necessitates a nephrectomy. However, the huge size of these kidneys makes a standard laparoscopic approach difficult, and the increased fragility of these patients makes an open nephrectomy risky. A compromise position has been found in the realm of hand-assisted laparoscopic techniques, especially for patients in need of a bilateral nephrectomy. Hand-assisted laparoscopic nephrectomy (HALN) is performed via a hand-assist device placed in the midline. A subxiphoid midline port and a midclavicular subcostal port are placed on the ipsilateral side. The right hand is inserted for left nephrectomy and the left hand for a right nephrectomy. The laparoscope is introduced into the subxiphoid port, and the surgeon's primary working instrument is passed via the midclavicular port. Occasionally, it is helpful to place a 5-mm subcostal port in the midaxillary line to aid in retracting the kidney. Once the kidney is devascularized, it is removed via the 7- to 8-cm hand-assist incision; drainage of cysts may be necessary during extraction to reduce the kidney size so that it can be withdrawn. If a bilateral approach is to be done, then after the first nephrectomy, the lateral 5-mm port is closed, and the table is rolled such that the contralateral side is elevated about 30 degrees to 45 degrees; a subcostal midclavicular 12-mm port is placed, and, if needed, a 5-mm port is inserted subcostally in the midaxillary line for renal retraction. Seven bilateral hand-assisted laparoscopic nephrectomy cases have been reported. In two reports, the mean operating times were 4.8 and 5.5 hours. The mean estimated blood loss was <350 mL. The hand-assisted laparoscopic approach makes both unilateral and bilateral nephrectomy feasible in ADPKD patients with acceptable morbidity.